Advances in antiretroviral (ARV) pharmacotherapy have translated to increased longevity and improved quality of life in people living with HIV; hence, elderly individuals comprise an increasing proportion of todays HIV population. Moreover, HIV infection itself has become recognized as a condition characterized by a hypercoaguable state and premature immunologic aging. Potential interactions between ARVs and anticoagulant medications are of particular concern considering that many elderly, and even non-elderly HIV patients will require short-term or chronic anticoagulation to prevent and/or treat systemic embolism. Dabigatran, administered as dabigatran etexilate, is an oral irreversible, competitive direct thrombin inhibitor, which has been shown to be superior to warfarin, and non-inferior to enoxaparin, in preventing thromboembolism in patients with atrial fibrillation and undergoing orthopedic surgery, respectively. While dabigatran itself is not a substrate of Permeability-glycoprotein (P-gp), its inactive pro-drug, dabigatran etexilate, is a substrate of P-gp. Co-administration of dabigatran etexilate with P-gp modulators has resulted in significant changes in dabigatran exposure. The pharmacokinetic enhancers, ritonavir and cobicistat, as inhibitors of P-gp, are expected to increase plasma concentrations of dabigatran; however, neither agent has been studied in combination with dabigatran etexilate, to date. Hence, the purpose of this study is to determine whether the separate co-administration of ritonavir or cobicistat with dabigatran etexilate increases the systemic exposure of dabigatran in healthy volunteers, and if so, whether adjusting the administration times of these medications can circumvent this interaction. In this open-label study, 32 healthy volunteers will be assigned to 1 of 2 groups. Group A will consist of 16 subjects who will take 22 days of ritonavir; Group B will consist of 16 subjects who will take 22 days of cobicistat. All subjects will receive 3 separated single doses of dabigatran etexilate. Pharmacokinetic (PK) and pharmacodynamics (PD) sampling for dabigatran will occur on Days 0 1, Day 191 20, and Day 261 27. The PD effects of dabigatran will be characterized via ecarin clotting time (ECT) measurements. Dabigatran PK/PD parameters will be determined using non-compartmental methods with the WinNonlin professional computer program (version 5.2; Pharsight Corporation, Mountain View, CA). The following PK/PD parameters will be compared between the groups: area under the curve from 0 to 24 hours (AUC0-24), maximum total dabigatran plasma concentration (Cmax), area under the curve from 0 to infinity hours (AUC0-&#8734;), time to maximum plasma concentration (tmax), terminal half-life (T), apparent oral clearance (CL/F), area under the effect curve from 0 to 24 hours (AUEC0-24), and the maximum effect ratio over baseline (ERmax). This study has completed enrollment of group A. Parttial data was presented at 15th International Workshop on Clinical Pharmacology in HIV and Hepatitis, Washington DC, May, 2014. Further data analysis and reporting is planned, including a manuscript for peer-reviewed publication. Enrollment of group B is being delayed by FDA approval of cobicistat as a single-agent therapeutic, which is expected to occur in October 2015, at which point we will be able to proceed with enrolling these patients.